An understanding of cellular regulatory mechanisms is fundamental to the solution of some of the most important problems in cell biology. Studies in bacterial systems that have sought to map the location of genes including those with regulatory functions have been of great heuristic value in understanding the genetic basis of regulation in those cells. In these studies we propose to use the methods of somatic cell hybridization and the phenomena that ensue following appropriate mouse-human somatic cell hybridization to perform mapping and complementation studies in the interferon system of human cells. The studies of regulation and localization will be aimed at clarification of some of the phenomena in the interferon system, a system whose regulation is apparent but not understood. Specifically, we plan to develop the following lines of inquiry using the indicated methodologies: 1. Experiments designed to establish as precisely as possible the chromosome or chromosomes involved in the induction of interferon. 2. Experiments designed to establish as precisely as possible the chromosome or chromosomes necessary for the induction of the antiviral state by interferon or synthetic polyribonucleotides. 3. Studies of the regulation of interferon biosynthesis in reduced hybrids and hybrids of reduced hybrids. 4. The development of selective systems based on the interferon response which will employ the species specificity of interferon to distinguish between hybrid clones and the clones of unhybridized parents. The technical problems posed by these proposals will be solved by application of what are now standard techniques of Beta-propriolactone mediated cell fusion, a variety of techniques of chromosome analysis, mechanical techniques of clone isolation and inteferon assay and where appropriate by use of replica plating.